Differential effects of benzodiazepines on cochlear and auditory nerve responses

Abstract

The influence exerted by chlordiazepoxide or midazolam upon auditory nerve compound action potential (cAP) and cochlear microphonic (CM) has been analyzed in chronic as well as in acutely prepared guinea pigs. Pre-receptorial variables were carefully controlled. The benzodiazepines dissociated the conchlear recroded potentials, increasing the cAP amplitude, in response to clicks, and decreasing the CM area, produced by a coherent pure tone pip. Both responses were dose related. A direct effect upon the cochlea was eliminated by local infusion of teh drugs. It was also demonstrated to be a specific benzodiazepines action because the use of an antagonist, Ro 15-1788, abolished the effect. Benzodiazepines could have increased the GABAergic activity at the pontine origins of the olivo-cochlear bundle or in the reticulo-cochlear fibers. These are the only central pathways that could be responsible for the effects obtained at the cochlea or auditory nerve levles. We suggest that this is cause of the withdrawal of inhibitory tonus from the primary afferent fibers mediated by the effrent system (lateral superior olive), as may occur during dishabituation. It may also be the cause of the CM decrenent, but the effect in this case would be exerted mainly through another set of efferent fibers (trapezoid body nucleus).